We have analyzed paired lung adenocarcinomas and adjacent non-tumor tissues from 60 patients who were less than 50, older than 79, or between 57-72 years of age at the time of diagnosis for the presence of LOH in five commonly affected chromosome arms including 3p, 3q, 9p, 17p, and 19p. Further genetic analyses pointed a 2 Mb region containing roughly 50 genes at chromosome 3p21.2 as the region most strongly associated with patients who had lung cancers younger than age 50. Our data is the first to provide direct evidence linking lung cancer susceptibility in extreme-age populations to a specific genetic alteration in the human genome. We are now sequence these candidate genes in primary tumors and the matched normal lungs to determine if mutations in these genes might contribute to lung cancer development. Additional studies are also underway to determine the cellular location of these genes and their potential molecular function in cell growth and tumor formation.